There is a large scale recirculation of lymphocytes between blood and lymph which occurs principally through lymph nodes and intestinal lymphoid tissues. Studies in murine animals have shown that lymphocytes leave the blood and enter into these tissues by association with a unique system of microvascular structures-the high endothelial venules (HEV). Investigation of the mechanism of this phenomenon will be accomplished through the use of a new in vitro assay system we have developed which permits direct observation and experimentation on the interaction between lymphocytes and endothelium of specialized venules of peripheral lymph nodes. The work will be performed using inbred mice and rats. Emphasis will be placed on delineating the cell populations which display HEV binding activity in vitro and the results correlated with the distributional properties of the cells in vivo, the object being to ascertain if surface receptors for HEV recognition are an exclusive property of recirculating lymphocytes. Lymphocytes cultured in vitro will be used to investigate turnover and production of HEV binding surface components and for isolation and structural characterization of these molecules. Metabolic and cytoplasmic events involved in lymphocyte-HEV adherence and dissociation will be studied. It is also planned to evaluate the influence of histoincompatibility on binding of lymphocytes to HEV endothelium. The effects of antigenic stimulation on the functional properties of HEV and adherence capabilities of lymphocytes will also be investigated.